MAST Trial: Multi-modal Analgesic Strategies in Trauma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MAST Trial: Multi-modal Analgesic Strategies in Trauma (NCT03472469), a randomized phase 4 study. The primary outcome is Opioid Use Per Day.

2. Clinical Question

The question is comparative effectiveness: the trial contrasts two care strategies rather than a strategy with no analgesic treatment. It is randomized, parallel-group and unmasked. The primary measure combines opioid doses by their morphine-equivalent dose and expresses that amount per day hospitalized. This makes the outcome a measure of average daily opioid exposure during the stated hospital period, not a measure of pain relief by itself.

3. Trial Design

The MAST Trial was a Phase 4 randomized, unmasked, parallel-group study. It compared the Original MMPR descending dose arm with the MAST MMPR escalating dose arm in people with nonspecific pain after traumatic injury. Enrollment was 1561. The registry lists The University of Texas Health Science Center, Houston as the sponsor. The recorded start date is 2018-04-02, the primary completion date is 2019-07-03, and the study status is completed.

The registry summary frames the study as a comparison of current pain-management strategies for acutely injured trauma patients. Both strategies are described as multimodal and opioid minimizing. The arm descriptions include scheduled medicines, but the descriptions in the registry record are truncated; the complete regimens, including all dosing and treatment rules, are not reported in the registry record. The record also does not report the randomization sequence method, concealment procedures, participating sites, or details of how treatment adherence was assessed.

The primary endpoint was opioid use per day, measured as median MME per day. It covered the period until hospital discharge or 30 days after admission, whichever occurred sooner. The posted arm results include 787 participants in the Original MMPR arm and 774 in the MAST MMPR arm. The registry also lists pain scores, opioid prescriptions at discharge, opioid-related complications, costs, ventilator days and hospital days among secondary outcomes. The available outcome information does not include detailed results for most of those measures.

Unmasked treatment assignment means participants and clinical staff were not blinded according to the registry entry. The record does not describe any masking of outcome assessors or analysts. It does not report the planned analysis populations, a sample-size justification for the trial, interim analyses, or the full statistical analysis plan. These omissions limit how fully the trial’s conduct and analysis choices can be evaluated from the registry record alone.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Opioid Use Per Day, measured over until discharge from hospital or 30 days post admission (whichever is sooner).

The primary endpoint is opioid use per day, reported in morphine milligram equivalents (MME per day). The registry defines it by tallying the dose equivalency of all opioids received and dividing by the number of days hospitalized. The observation period ends at hospital discharge or 30 days after admission, whichever occurs sooner. An MME measure allows different opioids to be expressed on a common dose-equivalency scale; the daily measure describes opioid exposure relative to time in hospital.

The registry reports the median and inter-quartile range for each arm. A median describes the middle of the observed values, while the inter-quartile range describes the spread from the lower to the upper quartile. These summaries can be useful when individual observations are unevenly distributed or include particularly high values, because the median is less affected by extreme observations than the mean. This is a general statistical explanation, not a claim about the shape of the trial’s data.

The outcome is a medication-use measure, not a direct measure of pain intensity, function, or patient preference. Dividing opioid exposure by hospital days also means the value is tied to the hospital observation period and its duration. The registry posts arm-specific medians of 48.0 MME per day (inter-quartile range 22.0 to 74.0) for the Original MMPR arm and 34.0 MME per day (15.0 to 61.0) for the MAST MMPR arm. A formal two-arm comparison for this primary endpoint is not reported in the registry record, so these summaries alone do not establish the precision or statistical uncertainty of the between-arm contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the median report?

The median is the value at the center of an ordered set of observations. It is a measure of location, not a measure of uncertainty about a treatment contrast. The inter-quartile range gives the lower and upper quartiles and describes the middle portion of the observed distribution. A broad range of values within an arm can coexist with a difference between arm medians, and overlapping inter-quartile ranges do not serve as a formal test of that difference. These are general statistical principles.

For the primary endpoint, the registry reports medians and inter-quartile ranges but does not report an inferential comparison between arms. The reported summary statistics therefore describe the groups without stating a confidence interval or p-value for the primary treatment contrast. A comparison of medians may require methods that account for the outcome’s distribution and the trial design; the particular method planned or used is not reported in the registry record.

What would a confidence interval contribute?

In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical procedure and its assumptions. For a between-arm effect, it helps readers assess precision and whether values representing no difference remain compatible with the data. It does not mean that there is a stated probability that the true effect lies inside the particular interval. No confidence interval for the primary endpoint is reported in the registry record, so the precision of a primary contrast cannot be assessed from the posted medians alone.

How should the secondary binary comparison be read?

The discharge-prescription outcome is a count of participants with the outcome in each arm. The registry posts a risk difference for MAST MMPR relative to Original MMPR, along with an unadjusted confidence interval and p-value. In general, a risk difference expresses the difference between the two arm-level proportions; its zero value corresponds to equal proportions. The posted estimate is negative, and its confidence interval is wholly below zero. The unadjusted p-value is 0.024. This is an unadjusted secondary comparison, not a result for the primary MME-per-day endpoint.

The registry also lists relative-risk and odds-ratio summaries for this secondary comparison. These are different ways to express an association between group and outcome. A relative risk compares proportions directly, while an odds ratio compares odds. Both can be useful, but their numerical meaning differs from that of a risk difference. None of these measures, on its own, accounts for testing multiple outcomes unless a multiplicity procedure is part of the analysis. The multiplicity approach is not reported in the registry record.

What do planning illustrations mean?

The sample-size illustrations use the observed secondary effect as a reference and show planning scenarios for detecting 100%, 75% or 50% of that effect. They use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The figures are planning illustrations, not the trial’s observed power and not evidence that the original trial was designed around those assumptions. The registry record does not report the trial’s own sample-size justification. In general, planning calculations estimate the number of participants needed under stated assumptions; they do not establish that an observed result is true or clinically important.

Planning for a smaller effect generally requires more participants than planning for a larger effect, if the other assumptions are held fixed. This is a general relationship, not a new calculation about this trial. The actual sample-size requirements also depend on the chosen outcome, analysis method, variability, allocation, significance threshold and target power. The registry’s illustrations use assumptions stated for those calculations, and should not be mistaken for a reconstruction of the trial’s original design process.

What analysis details remain unknown?

The registry identifies the trial as randomized, unmasked and parallel-group, but does not report the random sequence method or allocation concealment. It does not report whether the primary analysis used an intention-to-treat population, a per-protocol population, or another analysis set. It also does not describe missing-data methods, covariate adjustment, sensitivity analyses, or an interim-analysis plan. These details can affect how a reported estimate is interpreted, especially when outcome data are incomplete or treatment assignment and treatment received differ.

For the primary outcome, the registry reports no comparison analysis. For the secondary discharge-prescription outcome, the reported p-value is explicitly unadjusted. The registry does not state whether other analyses were conducted but omitted, whether a statistical plan prespecified the reported comparison, or how the family of secondary tests was handled. In general, testing multiple outcomes increases the chance that at least one result appears unusual by chance when each is assessed separately. That is why the analysis plan and any multiplicity approach are relevant to interpretation.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies 11 secondary outcomes, spanning pain, opioid prescribing and complications, costs, ventilator days and hospital days. The available record includes a detailed unadjusted comparison for the discharge-prescription outcome. The multiplicity procedure, if any, is not reported in the registry record. It is therefore not possible to determine whether the secondary analysis was intended to be confirmatory, whether results were adjusted for the number of outcomes, or whether a hierarchy or other testing strategy was prespecified.

In general, multiplicity matters because repeated testing can make apparently notable results more likely even when there is no underlying difference. A nominal p-value is interpreted under the test’s stated assumptions and does not automatically account for other tests. The posted secondary p-value is unadjusted, so it should be considered in that context. No multiplicity adjustment should be assumed from the registry entry.

Missing-data procedures are not reported in the registry record. The record does not describe how missing endpoint values were handled, whether the missingness differed between arms, or whether sensitivity analyses were conducted. It also does not identify the analysis population for the primary outcome. Randomization describes assignment to treatment groups, but it does not by itself specify which participants or measurements enter a particular analysis.

The record does not report whether the primary analysis was intention-to-treat, per-protocol or based on another population. It does not state whether participants were analyzed according to randomized assignment or treatment received. Interim analyses and stopping rules are also not reported in the registry record. These omissions do not establish that such methods were absent; they mean that the registry entry does not document them.

Without the analysis plan, missing-data details and population definitions, readers cannot fully assess the risk of selective analysis or the robustness of the posted secondary result. These are reporting limitations, not proof that the trial’s conduct was biased. The missing primary comparison is especially consequential because the primary endpoint is the central randomized comparison specified in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: death (4.7%).

The registry lists serious adverse events for both arms. The Original MMPR arm had 29 serious adverse events among 787 participants at risk, and the MAST MMPR arm had 36 among 774 participants at risk. The registry also lists 29 deaths in the Original MMPR arm and 36 in the MAST MMPR arm. Death is the serious-event term listed in the record, at 4.7%.

These counts describe what the registry reports; they do not establish that the study treatments caused the deaths or serious adverse events. The registry record does not provide a causal attribution, a comparative safety analysis, or uncertainty estimates for the between-arm difference in serious events. It lists zero other adverse events in each arm under the other-event fields, but this should be read as a registry entry rather than as proof that no other events occurred outside the reported classification.

Event counts should be interpreted with the number at risk and the way events were collected in mind. The registry does not report detailed event definitions, timing, severity criteria beyond the serious-event category, or the adjudication process. The posted figures are therefore a descriptive safety record, not a complete assessment of comparative risk.

12. What the Result Does, and Does Not, Mean

The primary result establishes that the registry reports different arm-specific medians for daily opioid use during the stated hospital period. It does not establish the size or precision of a formal between-arm effect because the registry does not report an estimable two-arm comparison for the primary endpoint. The inter-quartile ranges describe the spread within each arm; they are not confidence intervals for the difference between arms.

The trial was randomized, which makes a treatment-strategy comparison its central design question. But randomization alone does not fill in missing reporting about the analysis method, analysis population, outcome completeness or uncertainty around the primary result. Without a reported primary comparison, the posted summaries cannot answer how compatible the observed data are with a range of possible treatment contrasts.

The secondary discharge-prescription result concerns a different endpoint. Its direction and unadjusted inferential statistics are posted, but the result does not directly determine daily inpatient opioid use, pain, or other outcomes. The registry does not report comparative results for most of the stated secondary outcomes, and it does not report a multiplicity procedure. This limits the extent to which the secondary finding can be treated as confirmatory evidence across the study’s broader questions.

The findings do not establish that one strategy is clinically preferable, that either strategy reduces pain, or that either strategy is safer. The registry’s primary outcome measures opioid amount per hospital day, not pain relief or patient-centered benefit. Nor do arm-specific summaries demonstrate causation in isolation or resolve uncertainty about missing data and analysis choices. The most defensible reading is descriptive: the posted medians and the secondary prescription comparison are observations from this randomized trial, with important gaps in the reported primary inference and broader outcome results.

These limits do not negate the information in the record. They define what can and cannot be concluded from it. The trial’s question and measured outcomes are clear, but the complete statistical basis for interpreting its primary comparison is not reported in the registry record.

13. Why This Trial Matters Statistically

This trial raises a useful statistical issue: a randomized study can post arm-level summaries for its primary endpoint without posting the comparative estimate needed to assess uncertainty. Readers can see the median and inter-quartile range in each arm, but those summaries do not substitute for an estimate and confidence interval for the randomized contrast. Reporting the contrast is important because the scientific question concerns how outcomes compare between strategies, not only what each group’s median was.

The endpoint also illustrates the distinction between a measure of treatment exposure and a measure of patient experience. MME per day quantifies opioid use on a common equivalency scale over the hospital period. Pain scores and discharge prescriptions address related but separate questions. Considering the outcome definitions carefully helps prevent an inference about one construct from being carried over to another.

The record also makes multiplicity relevant. A trial may assess multiple secondary outcomes, and a nominally notable unadjusted result needs to be interpreted in the context of the testing plan. Without a reported multiplicity strategy and without comparative results for most secondary outcomes, it is difficult to judge how the available secondary finding fits into the full analysis.

Finally, the study shows why completeness of statistical reporting matters alongside the design label. Randomization is central to a fair comparison, but interpretation also depends on analysis populations, missing-data handling, prespecified methods and uncertainty estimates. Those details are not reported in the registry record. Clear reporting of them would help readers distinguish descriptive patterns from supported comparative conclusions.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpretation is that the registry posts medians and inter-quartile ranges but no estimable two-arm comparison for the primary endpoint. There is consequently no reported primary confidence interval or p-value with which to assess uncertainty. Readers should not infer statistical significance or precision from the arm summaries alone.

The registry’s descriptions of the two treatment regimens are incomplete, and the complete schedules are not reported in the registry record. This limits the ability to understand exactly how the strategies differed in practice. The entry also does not report the randomization procedure, allocation concealment, study sites, adherence assessment, or whether outcome assessors were masked.

Several analytic details are not reported in the registry record, including the primary analysis population, missing-data methods, adjustment variables, sensitivity analyses, interim analyses and the trial’s own sample-size justification. The available planning illustrations are not the trial’s documented design rationale. The unadjusted secondary comparison also lacks a reported multiplicity approach, while comparative estimates for most listed secondary outcomes are not reported.

The primary outcome is limited to opioid use during hospitalization or the stated maximum follow-up period. It is not itself a measure of pain, functional recovery or longer-term opioid use. The registry does list pain outcomes, but their comparative results are not reported in the available record. Safety figures are descriptive, with no reported causal attribution or comparative uncertainty analysis.

These are limitations of the information available in the registry record and should not be mistaken for proof that the trial was poorly conducted. They do, however, constrain independent assessment of the primary result and the overall balance of outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: MAST Trial: Multi-modal Analgesic Strategies in Trauma — NCT03472469.
• Registry record last updated 2021-06-18; status last verified 2021-06.
• Results first posted 2021-06-10.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT03472469 is the completed Phase 4 MAST Trial, a randomized, unmasked, parallel-group comparison of the Original MMPR descending dose arm and the MAST MMPR escalating dose arm in acutely injured trauma patients with nonspecific pain after traumatic injury. Enrollment was 1561. The sponsor was The University of Texas Health Science Center, Houston.

The primary outcome was median opioid use per hospital day, measured in MME per day until discharge or 30 days after admission, whichever occurred sooner. Arm-specific medians and inter-quartile ranges are posted, but a two-arm comparison for the primary endpoint is not reported in the registry record. The registry lists 11 secondary outcomes and includes an unadjusted comparison for discharge with an opioid prescription; comparative results for most other secondary outcomes are not reported.

The record lists serious adverse events and deaths in both arms. Analysis populations, missing-data methods, the trial’s sample-size justification and the multiplicity approach are not reported in the registry record.